In Vitro Immunotoxicity of Organophosphate Flame Retardants in Human THP-1-Derived Macrophages

Scarce attention has been paid to the immunotoxicity of organophosphate flame retardants (PFRs), which poses a challenge to the systematic assessment of their health risks. In this study, a battery of in vitro immunotoxicity screening assays, including adhesion, phagocytosis, and 48 cytokine/chemokine production, was measured after exposing THP-1-derived macrophages to six selected common PFRs (TPHP, TDCPP, TNBP, TOCP, TCEP, and TBOEP) at a noncytotoxic concentration (≤50 μM). Our results showed that TPHP and TBOEP partially attenuated the adhesion and phagocytosis of the THP-1 mφs and that TDCPP caused a functional loss of phagocytosis, implying the potential immunosuppression. In contrast, TNBP and TOCP may cause an immunostimulation by significantly promoting cell adhesion and enhancing phagocytic efficiency. Additionally, the results from a cytokine/chemokine secretion analysis revealed the proinflammatory properties of TDCPP, TPHP, and TBOEP. TOCP was thought to disrupt the inflammatory balance by inhibiting both proinflammatory and antiinflammatory cytokines. TCEP showed no effect on adhesion or phagocytosis and little modulation of cytokine release at this experimental concentration. Overall, this study supports that PFRs can be immunotoxic to macrophages in different ways and provides evidence for developing more sensitive in vitro immunotoxicity bioassay methods.